Impaired Kynurenine Pathway Metabolism in The Prefrontal Cortex of Individuals With Schizophrenia
Korrapati V. Sathyasaikumar,Erin K. Stachowski,Ikwunga Wonodi,Rosalinda C. Roberts,Rosalinda C. Roberts,Arash Rassoulpour,Robert P. McMahon,Robert Schwarcz +7 more
TLDR
The present results further support the hypothesis that the normalization of cortical KP metabolism may constitute an effective new treatment strategy in SZ.Abstract:
The levels of kynurenic acid (KYNA), an astrocyte-derived metabolite of the branched kynurenine pathway (KP) of tryptophan degradation and antagonist of α7 nicotinic acetylcholine and N-methyl-D-aspartate receptors, are elevated in the prefrontal cortex (PFC) of individuals with schizophrenia (SZ). Because endogenous KYNA modulates extracellular glutamate and acetylcholine levels in the PFC, these increases may be pathophysiologically significant. Using brain tissue from SZ patients and matched controls, we now measured the activity of several KP enzymes (kynurenine 3-monooxygenase [KMO], kynureninase, 3-hydroxyanthranilic acid dioxygenase [3-HAO], quinolinic acid phosphoribosyltransferase [QPRT], and kynurenine aminotransferase II [KAT II]) in the PFC, ie, Brodmann areas (BA) 9 and 10. Compared with controls, the activities of KMO (in BA 9 and 10) and 3-HAO (in BA 9) were significantly reduced in SZ, though there were no significant differences between patients and controls in kynureninase, QPRT, and KAT II. In the same samples, we also confirmed the increase in the tissue levels of KYNA in SZ. As examined in rats treated chronically with the antipsychotic drug risperidone, the observed biochemical changes were not secondary to medication. A persistent reduction in KMO activity may have a particular bearing on pathology because it may signify a shift of KP metabolism toward enhanced KYNA synthesis. The present results further support the hypothesis that the normalization of cortical KP metabolism may constitute an effective new treatment strategy in SZ.read more
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Journal ArticleDOI
Association of the kynurenine pathway metabolites with clinical, cognitive features and IL-1β levels in patients with schizophrenia spectrum disorder and their siblings
Handan Noyan,Ece Erdağ,Erdem Tüzün,Ilhan Yaylim,Ozlem Kucukhuseyin,Mehmet Tolgahan Hakan,Sinan Guloksuz,Bart P. F. Rutten,Meram Can Saka,Cem Atbaşoğlu,Köksal Alptekin,Jim van Os,Alp Üçok +12 more
TL;DR: In this article, the authors investigated whether TRP-kynurenine dysregulation occurs in advanced stages of the disease as a byproduct or emerges as one of the early and inherited manifestations of schizophrenia.
Journal ArticleDOI
Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology.
Amira Ben Afia,Èlia Vila,Karina S. MacDowell,Karina S. MacDowell,Aida Ormazabal,Juan C. Leza,Juan C. Leza,Josep Maria Haro,Rafael Artuch,Belén Ramos,Belén Ramos,Borja García-Bueno,Borja García-Bueno +12 more
TL;DR: In this article, the kynurenine pathway has been linked to alterations in glutamatergic and monoaminergic neurotransmission and to SZ symptomatology through the production of the metabolites quinolinic acid (QA) and kynurenic acid (KYNA).
Journal ArticleDOI
Repeated administration of LPS exaggerates amphetamine-induced locomotor response and causes learning deficits in mice
Maximilian Tufvesson-Alm,Sophie Imbeault,Xi Cong Liu,Yiran Zheng,Anthi Faka,Doo Sup Choi,Lilly Schwieler,Göran Engberg,Sophie Erhardt +8 more
TL;DR: It is shown that repeated LPS administration increases sensitivity to D-amphetamine and produces cognitive deficits and anxiety-like behavior, and may be useful to study the contribution of inflammation to psychiatric disorders such as schizophrenia.
Book ChapterDOI
The Role of Inflammation and the Immune System in Schizophrenia
TL;DR: Support for the inflammatory hypothesis comes from the therapeutic benefit of anti-inflammatory medications in specific studies and the intrinsic anti- inflammatory and immunomodulatory effects of antipsychotic drugs.
Trends in Psychiatry and Psychotherapy
TL;DR: The adaptation of a revised Brazilian version of the Patient Competency Rating Scale (PCRS-R-BR), which focuses on executive, management, and decision-making skills, is described.
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